Uncovering the role of apolipoprotein C-III in insulin resistance
Clin Investig Arterioscler. 2021 Mar-Apr;33(2):108-115.
doi: 10.1016/j.arteri.2020.09.003.
Epub 2020 Dec 8.
[Article in
English,
Spanish]
Affiliations
- 1 Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Institute of Biomedicine of the University of Barcelona (IBUB), Spain; Spanish Biomedical Research Center in Diabetes and Associated Metabolic Diseases (CIBERDEM)-Instituto de Salud Carlos III, Spain; Research Institute-Hospital Sant Joan de Déu, Barcelona, Spain.
- 2 Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Institute of Biomedicine of the University of Barcelona (IBUB), Spain; Spanish Biomedical Research Center in Diabetes and Associated Metabolic Diseases (CIBERDEM)-Instituto de Salud Carlos III, Spain; Research Institute-Hospital Sant Joan de Déu, Barcelona, Spain. Electronic address: mvazquezcarrera@ub.edu.
Abstract
Apolipoprotein C-III (apoC-III) is a small protein that is predominantly synthesized in the liver and mainly resides at the surface of triglyceride-rich lipoproteins. Its expression is upregulated by glucose and reduced by insulin, with enhanced apoC-III promoting hypertriglyceridemia and inflammation in vascular cells. The protein is also elevated in patients with diabetes, suggesting that enhanced apoC-III levels might contribute to the development of type 2 diabetes mellitus. The present review focuses on the key mechanisms by which apoC-III could promote type 2 diabetes mellitus, including exacerbation of insulin resistance in skeletal muscle, activation of β-cell apoptosis, promotion of weight gain through its effects on white adipose tissue and hypothalamus, and attenuation of the beneficial effects of high-density lipoproteins on glucose metabolism. Therapeutic strategies aimed at reducing apoC-III levels may not only reduce hypertriglyceridemia but also might improve insulin resistance, thus delaying the development of type 2 diabetes mellitus.
Keywords:
ApoC-III; Atherogenic dyslipidemia; Dislipemia aterogénica; Insulin resistance; Resistencia a la insulina.
Copyright © 2020 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.
MeSH terms
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Animals
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Apolipoprotein C-III / genetics
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Apolipoprotein C-III / metabolism*
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Diabetes Mellitus, Type 2 / physiopathology*
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Diabetes Mellitus, Type 2 / prevention & control
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Gene Expression Regulation
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Glucose / metabolism
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Humans
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Hypertriglyceridemia / physiopathology
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Hypertriglyceridemia / prevention & control
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Insulin / metabolism
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Insulin Resistance / physiology*
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Lipoproteins, HDL / metabolism
Substances
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Apolipoprotein C-III
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Insulin
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Lipoproteins, HDL
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Glucose